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Total Chemical Protein Synthesis for the Determination of Novel X-ray Structures by Racemic Protein Crystallography

机译:外消旋蛋白质晶体学用于测定新型X射线结构的总化学蛋白质合成

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Total synthesis of proteins by modern chemical ligation methods enables the ready preparation of high purity protein molecules of typical size (up to ~300 amino acid residues). This in turn enables the preparation of mirror image D-protein molecules not found in nature. Use of a racemic protein mixture (i.e. D-protein + L-protein) greatly facilitates the formation of diffraction-quality crystals of otherwise recalcitrant proteins. Facilitated crystallization is also observed for quasi-racemic protein mixtures. Centrosymmetric crystals of racemic proteins diffract to high resolution and offer enhanced possibilities for structure solution by direct computational methods. Racemic protein crystallography has been successfully applied to a number of recalcitrant protein molecules, and has been used to determine the structure of a 35 kDa {L-protein target/D-protein ligand} complex.
机译:通过现代化学连接方法进行蛋白质的全合成,可以随时准备典型大小(最多约300个氨基酸残基)的高纯度蛋白质分子。这继而使得能够制备自然界中未发现的镜像D蛋白分子。外消旋蛋白混合物(即D蛋白+ L蛋白)的使用极​​大地促进了其他顽固蛋白的衍射质量晶体的形成。准外消旋蛋白质混合物也观察到促进结晶。外消旋蛋白质的中心对称晶体衍射至高分辨率,并通过直接计算方法为结构求解提供了增强的可能性。外消旋蛋白晶体学已成功地应用于许多顽固蛋白分子,并已用于确定35 kDa {L蛋白靶标/ D蛋白配体}复合物的结构。

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